Infertility is problem affecting many couples with a child wish, affecting almost 15% of all couples. In these couples, half of these problems can be attributed from the male.
Infertility is defined as being unable to get pregnant despite having frequent, unprotected sex for at least a year. In almost 20% of male patients, a chromosomal or genetic defect can be identified. This research investigation will be focusing on male’s infertility and if X-linked genetic abnormalities increase their risk. The X-chromosome is a frequent interest in the genetic study of male infertility, this is due to males only having one X- chromosome. This means mutations in an X-linked gene would not be covered by a normal allele and thus would be evident in males.
This investigation will primarily focus on understanding whether males only having one X-chromosome (no compensatory allele), means that they are at risk of infertility due to X-linked, recessive disorders. The research investigation first had a broad claim of ‘Biological males are less susceptible to infertility problems than biological females.’ To narrow the focus, the study will be analysing the X-linked genetic abnormalities of the deletion of the TEX11 of chromosomes (Consequence of too little X), Klinefelter Syndrome (Consequence of too much X) and the amount of infertility problems, due to genetic abnormalities compared to women.
Klinefelter’s syndrome is caused by an extra copy of the X chromosome in each cell (XXY) and having ‘too much’ of the X-Chromosome. Klinefelter’s syndrome causes problems with male’s testicles and prevents them from making enough normal sperm, resulting in 95-99 % of those with the syndrome to struggle with infertility. This genetic abnormality occurs in 1:600 male newborns and is the most frequent form of failure in production of the testis. An investigation was conducted to find more research on male infertility, and in this case Klinefelter’s Syndrome in azoospermia infertile males. Azoospermia is the medical condition of a man whose semen contains no sperm and is associated with infertility, but many forms are amenable to medical treatment. The investigation is also aimed to find more research, as much information about X-chromosomes and infertility as most of this study is still unknown. 30 azoospermia infertile males from AVBR hospital in India were selected for a study to find the percentage of Klinefelter’s syndrome in azoospermia infertile males and analysed in a cytogenic laboratory.
Findings from the investigation resulted in 3 of the 30 azoospermia infertile subjects to have chromosomal abnormalities of 47 chromosomes. This means 3 of the subjects had an aneuploidy number of chromosomes, as the usual number is only 46 for all men. This means they have XXY (Klinefelter’s syndrome), as shown in Table 1, resulting in 10% of the subjects to be diagnosed with the syndrome. The karyotype, which is a picture of a person’s chromosome was found and showed there was a numerical aberration with an extra ‘X’ chromosome which was suggestive of the Klinefelter’s syndrome. This data was confirmed using the G-banding technique which produces the visible karyotype by staining condensed chromosomes (Table 3). However, the remaining 90% of subjects had a normal chromosomal count of 46 (XY) and did not have a genetic abnormality in this area of study.
Hence, it can be concluded that without X-linked genetic abnormalities and mutations relating to Klinefelter’s syndrome, there would not be any infertility problems with men. This means that these mutations do increase a male’s risk of infertility and have a 10% chance of being diagnosed as shown in the investigation above.
However, a limitation of this data is the size of the cohort, the tests only included 30 subjects, and a larger data base would give more data to analyse. The investigation did include that the Klinefelter’s syndrome does increase a male’s risk of infertility, but the extent of this hasn’t been finalised, which means the conclusion can’t be drawn with confidence.
Testis-expressed gene 11 (TEX11), a different genetic abnormality, is an X-linked gene and is essential for meiotic, a form of cell division recombination and chromosomal synapsis. As males are hemizygous for the X-chromosome, meaning that there are only half as many alleles as normally present for a diploid individual, mutations in a single-copy X-linked genes cannot be compensated by the other X-chromosome. Therefore, mutations in X-linked genes, such as TEX11 gene is essential for male fertility mutations in men, as the gene causes meiotic arrest in males resulting in azoospermia. Since TEX11 is essential for meiotic recombination and chromosomal synapsis and TEX11 also causes meiotic arrest and male infertility, the identification of TEX11 mutations has become important to determine the underlying causes of male infertility, especially in men with azoospermia. A pedigree was conducted of an azoospermia male patient and his family, to help understand this X-linked mutation in TEX11.
The pedigree (family tree) shown in figure 3 demonstrates that only men have been diagnosed with azoospermia, including patient WHT3759, also meaning that this genetic abnormality is very likely to be from an X-chromosome. Males are more susceptible to inherit this mutation as they only have one X-chromosome unlike the mother who didn’t show any symptoms, meaning she is symptomatic as she has two (XX) chromosomes. Therefore, this X-linked genetic abnormality of the TEX11 gene in figure 3 can confirm that it does increase a male’s risk of infertility, due to having only one X-chromosome.
However, the data indicates a certain limitation such as, the trend would not continue, as the graph only shows one family pedigree. If more family data were collected it would show that not all male infertility places are affected by the TEX11 mutation, meaning the investigation research question cannot be answered with assurance. -either talk about a third mutation or answer claim and compare it to females
- Limitation is only 2-3 x-linked genetic abnormalities were analysed, meaning the question can’t be made focusing on all X-linked genetic mutations and if they increase a biological male’s risk of infertility
- most limitation include the investigation only focuses on 1 family, meaning if more family’s came into the equation the results may not be the same, may just be a ‘fluke’ of data
- extension can include making a bigger experiment with all patients with azoospermia to connect and maybe examine all the x-linked genetic conditions and compare with them to see if x-linked do increase a male’s risk of infertility
- Gajanan, L 2016, Klinefelter’s syndrome in azoospermia infertile males of Vibarbha region, Central India, viewed 10 June 2020, https://www.msjonline.org/index.php/ijrms/article/view/647
- Yanwei, S 2018, A novel TEX11 mutation induces azoospermia: a case report of infertile brothers and literature review, viewed 10 June 2020, https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-018-0570-4
- Androl, J 2019, Regulation of male infertility by X-linked genes, viewed 10 June 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931805/
- Vockell, M 2019, The X chromosome and Male Infertility, viewed 10 June 2020, https://link.springer.com/article/10.1007/s00439-019-02101-w